Diagnosis of leptomeningeal carcinomatosis (LMC) is made based upon the findings on MRI (LMCi), and/or cytologically confirmed cancer cells in the cerebrospinal fluid (CSF) (LMCc). However, in EGFR-mutated (EGFRm) cases, brain metastasis (BM) has a tendency to arise close to CSF space, and discrepancies between imaging and cytological results makes it difficult to construct treatment strategy. Although the effect of tyrosine kinase inhibitors (TKIs) on LMC has been expected, a little is known regarding the effect and limitation of TKIs.
Overall survival (OS) after diagnosis of BM were compared between patients with and without LMC at diagnosis, and prognostic value of LMCi and LMCc were retrospectively compared to clarify the reliable diagnostic method of LMC. Survival differences of patients with LMC after treatment with and without TKIs were also compared to evaluate the efficacy of TKIs on LMC.
From Aug. 2006 to now, 215 BMs from EGFRm non-small cell cancers were treated. At diagnosis of BMs, LMCi was diagnosed in 140 cases. Among these cases, CSF cytology was evaluated in 113 cases, but malignant cells were detected only in 47 cases (41.6%). TKIs were administrated in 159 patients. Without TKIs, OS after BM with LMCi (9.5m) was shorter than that without LMCi (26.9m) (HR: 1.75, P=0.096), but this difference was reduced in patients treated with TKIs (18.1m vs. 20.9m, P=0.123). On the other hand, without TKIs, OS after BM with LMCc (4.9m) was extremely worse than that without LMCc (16.6m) (HR:7.76, P=0.001), but this significant difference was lost by TKIs (HR:1.16, P=0.671). During the follow up, 152 deaths were observed, and 45 were owing to the progression of intracranial lesions (CNS death). Not LMCi but LMCc was a significant risk factor of CNS death (OR: 0.59 and 6.26, P=0.148 and 0.002, respectively). TKI had decreased the incidence of CNS death from 100% to 64% in LMCc cases, but LMCc was still a significant risk factor of CNS death even with TKIs (OR: 5.13, P=0.017), and disappearance of cancer cells in CSF by TKIs was observed only in 41.2% of patients.
MRI was insufficient to diagnose LMC. TKIs were strongly recommended for patients with LMCc, but its’ effect was still inadequate in half of the patients.
Clinical trial identification
Legal entity responsible for the study
Chiba Cancer Center
All authors have declared no conflicts of interest.